Linked Life Data

17012252

Source:http://linkedlifedata.com/resource/pubmed/id/17012252

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2006-10-2
pubmed:abstractText
Autosomal dominant Parkinson disease (PD) is caused by duplication or triplication of the alpha-synuclein gene as well as by the A30P, E46K, and A53T mutations. The mechanisms are unknown. Reactive astrocytes in the substantia nigra of PD and MPTP-treated monkeys display high levels of the inflammatory mediator intercellular adhesion molecule-1 (ICAM-1), indicating that chronic inflammation contributes to the degeneration. Here we report that alpha-synuclein strongly stimulates human astrocytes as well as human U-373 MG astrocytoma cells to up-regulate both interleukin (IL)-6 and ICAM-1 (ED50=5 microg ml(-1)). The mutated forms are more potent stimulators than wild-type (WT) alpha-synuclein in these assays. We demonstrate by immunoblotting analysis that this up-regulation is associated with activation of the major mitogen-activated protein kinase (MAPK) pathways. It is also attenuated by PD 98059, an inhibitor of the MAPK/extracellular-regulated kinase kinase MEK1/2, SP 600125, an inhibitor of c-Jun N-terminal kinase (JNK), and SB 202190, an inhibitor of p38 MAPK. The inhibitory effects on human astrocytes have IC50 values of 2, 5, and 1.5 microM respectively. We hypothesize that the neuroinflammation stimulated by release of an excess of normal alpha-synuclein or by release of its mutated forms can be involved in the pathobiology of PD.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1530-6860
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2000-8
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Alpha-synuclein and its disease-causing mutants induce ICAM-1 and IL-6 in human astrocytes and astrocytoma cells.
pubmed:affiliation
Kinsmen Laboratory of Neurological Research, University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC V6T 1Z3, Canada. aklegeri@interchange.ubc.ca
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't